Projects and Grants
Authentic Cellular Models
To study host-virus interactions, decipher viral replication strategies, unravel pathogenesis mechanisms, and pave the way for innovative therapeutic approaches, we use complex and authentic cellular models that encompass various cell types and reflect physiological processes in human biology. The current gold standard for studying respiratory pathogens such as SARS-CoV-2 are two-dimensional models based on primary airway epithelial cells (Airway Epithelial Cultures (AEC)), which are grown at an air-liquid interface (ALI) and closely resemble the molecular and functional aspect of the human respiratory epithelium and its multiple cell types in "pseudostratified" cell layers. Furthermore, we have generated 3-dimensional lung and brain organoids from induced pluripotent stem cells (iPS). These organoids offer a versatile platform for a wide spectrum of research questions and for personalized medicine approaches.
By integrating newly acquired kinetic data, we aim to construct a dynamic mathematical model that elucidates the intracellular processes of SARS-CoV-2 infection, replication, and assembly. Thanks to our expertise in the reverse genetics of coronaviruses, we can precisely modify viral proteins and study changes in replication dynamics to complement mathematical modeling. With the help of this model, we intend to investigate viral replication strategies, identify factors that influence the balance between viral replication and the antiviral immune response, and evaluate potential antiviral intervention strategies using computer and mathematical simulations.
Host Restriction Factors
Another focus of our research group is on understanding immunoreactivity against viruses, with a particular emphasis on interferons (IFN) and interferon-stimulated genes (ISG). We have already made important contributions to the identification and characterization of the interferon-stimulated gene LY6E and evaluated its mechanistic role both in vitro and in vivo regarding its significance (experimental cell time of non-coding RNAs, ncRNAs) to investigate their role in coronavirus restriction and immune control. These ncRNAs exert a significant influence on various cellular processes and have already been thoroughly studied in areas such as cancer research and cardiac biology. Accumulating evidence suggests that they play a central role in regulating infections and immune responses. As part of the DFG's Emmy Noether Programme, we are now focusing on this area of research to identify new coronavirus restriction factors. We have already demonstrated the positive influence of ex-LncRNA on the infection and replication of coronaviruses. We are now focusing on the exploration and characterization of further ncRNAs in connection with CoV infection and immune control.
Translation
Mit Heinrich und Anne Stegberg Stiftung und dem Preis für translationale Medizin in Zusammenarbeit mit der Kinderklinik des St. Joseph Krankenhaus (Ruhr-Universität Bochum) der Basis von Atemviren bei der Übertragung von Atemwegsviren, insbesondere bei Kindern. In einer unserer jüngsten Arbeiten haben wir, ausgelöst durch klinische Beobachtungen von Leberschäden nach einer SARS-CoV-2-Infektion, die molekularen Mechanismen analysiert, die diesen Prozessen zu Grunde liegen, und festgestellt, dass Hepatozyten anfällig für eine SARS-CoV-2 Infektion sind, welche von robusten entzündlichen Mikroreaktionen begleitet wird.
